Diabetes mellitus is a disease of a major global importance. The number of individuals affected increases at almost epidemic rates, such that in 2006, this number reached approximately 170 million people worldwide and is predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone-insulin. Within healthy pancreas, beta cells that are located in the islets of Langerhansand continuously produce and secrete insulin according to the blood glucose levels, thereby maintaining near constant levels of glucose in the body. Long-term tissue complication affects both the small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and the large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). These complications heavily burden the patients and health care resources that are necessary to treat the patients.
The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of chronic complications of diabetes are heavily related to the degree of altered glycemia, as quantified by determinations of glycohemoglobin (HbA1 c). [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia, which may be accomplished by frequently measuring glucose levels and accordingly adjusting an amount of delivered insulin, is of utmost importance.
Conventional insulin pumps can deliver insulin to the patient and can be configured to deliver rapid-acting insulin 24 hours a day through a catheter placed under the skin. The total daily dose (TTD) of insulin can be divided into basal and bolus doses. Basal insulin is delivered continuously over 24 hours and keeps the blood glucose concentration levels (hereinafter, “blood glucose levels”) in normal desirable range between meals as well as overnight. Diurnal basal rates can be pre-programmed or manually changed according to various daily activities of the patient. Insulin bolus doses are delivered before meals or during episodes of high blood glucose concentration levels to counteract carbohydrates' loads.
The amount of insulin which should be present in the administered bolus can depend on several parameters, for example:                Amount of carbohydrates (“Carbs”) to be consumed, alternatively defined as “serving”, wherein 1 serving equals 15 grams of Carbs.        Carbohydrate-to-insulin ratio (“CIR”), i.e. an amount of carbohydrate balanced by one unit of insulin which is measured in grams per one unit of insulin.        Insulin sensitivity (“IS”), i.e. an amount of blood glucose value lowered by one unit of insulin which is measured in mg/dL (milligrams/deciliter) per one unit of insulin.        Current blood glucose levels (“BSC”) which is measured in mg/dL.        Target blood glucose levels (“TBG”), i.e. a desired blood glucose level. TBG for most patients suffering from diabetes is in the range of 90-130 mg/dL before a meal, and less than 180 mg/dL one to two hours after the start of a meal.        Residual insulin, i.e. an amount of stored active insulin remaining in the body of the patient after a recent bolus delivery. This parameter is relevant when there is a short time interval between consecutive boluses (i.e. less than 5 hours).        
Conventional insulin pumps can require users to constantly calculate or estimate appropriate pre-meal insulin bolus doses. These calculations or estimations can be based on the above mentioned parameters to effectively control the blood glucose levels and maintain euglycemia.
Conventional portable insulin pumps can include bolus calculating means that operate based on inputs of meal carbohydrate content and glucose levels by the patient. In these pumps, the calculated bolus dose can be automatically delivered to the patient.
An example of such conventional pumps is discussed in U.S. Pat. No. 6,936,029 assigned to Medtronic MiniMed. Such a pump provided with a bolus calculator and an algorithm for calculating the amount of insulin to be administered is described. The algorithm is based on a formula for calculating a bolus, depending on the user's IS, CIR, target BG and user inputs of blood glucose (BG) and carbs intake.                If the current BG is higher than the target BG, the recommended bolus is calculated as:        
      Recommended    ⁢                  ⁢    bolus    =                    (                  TC          ⁢                      /                    ⁢          CIR                )                    ︸                                                                    ″                    ⁢          Food          ⁢                                          ⁢                      estimate            ″                                +                                                      (                              BSC                -                BST                            )                        ⁢                          /                        ⁢            IS                    -                          ︸                                                                                ″                        ⁢            Correction            ⁢                                                  ⁢                          estimate              ″                                          ⁢      RI      
Wherein TC—total amount of carbohydrates; CIR—carbohydrate-to-insulin ratio; BST—target blood sugar; BSC—current blood sugar; IS—Insulin sensitivity; RI—remaining insulin, i.e. “insulin on board”.                If the current BG is lower than the target BG, the recommended bolus is calculated as:Recommended bolus=(TC/CIR)+(BSC−BST)/IS        If the current BG is higher than the low target BG and lower than the high target BG (e.g. current blood (BSC) glucose=105 mg/dL, target range (BST)=90-130 mg/dL) then the recommended bolus is calculated as:Recommended bolus=(TC/CIR)+0        
Basal insulin can be delivered continuously over 24 hours, and can keep the blood glucose levels in range between meals and overnight. Diurnal basal rates can be pre-programmed or manually changed according to various daily activities. The basal insulin strongly depend on the user's IS value.
Accurate assessment of the IS value can be critical for maintaining euglycemia for diabetic patients. IS can also be essential in determination of the administered basal dose and the administered bolus dose, especially the correction bolus.
Currently, many type 1 diabetes patients using rapid acting insulin (e.g. Humalog, Novolog) determine their IS value according to the “2200 to 1600 rules”. The user's IS is established by dividing the value corresponding to an appropriate rule by the total daily dose of rapid-acting insulin (e.g. if the total daily insulin dose is 40 units and the 1800 rule is used, the insulin sensitivity factor would be 1800 divided by 40=45 mg/dl/unit). FIG. 1 shows the point drop per unit of insulin (insulin sensitivity) according to the various rules (adapted from Using Insulin ©2003)
The derived IS value can be used when initially setting the basal dosages and the bolus calculator of many existing pumps or when the user calculates the necessary bolus. Evaluation of the diabetic progression, especially in type 2 diabetes (insulin sensitivity is inversely related to insulin resistance, the primary etiology of type 2 DM), may be derived from the change in IS value (decreases as the disease progresses).
Using the abovementioned “rules” can have several drawbacks:                The accurateness of the established IS value is low due to a limited number of applied “rules”.        The values are not re-evaluated throughout the usage of the bolus calculator. This poses a serious problem since the IS value is not a static parameter. This shortcoming may be especially significant for adolescent users due to relatively frequent dynamics of this parameter during puberty.        